芪丹糖肾颗粒治疗糖尿病肾病机制的网络药理学研究  

Mechanism of Qidan Tangshen Granules in the Treatment of Diabetes Nephropathy Based on Network Pharmacology

作　　者：夏诗思 丛亿蕾 吴腾飞[1] 杨华[1] XIA Shisi;CONG Yilei;WU Tengfei;YANG Hua(Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai,China 200032)

机构地区：[1]上海中医药大学附属龙华医院,上海200032

出　　处：《中国药业》2024年第12期36-42,共7页China Pharmaceuticals

基　　金：上海市科技计划项目[20Y21902500]。

摘　　要：目的探讨芪丹糖肾颗粒治疗糖尿病肾病(DN)的作用机制。方法通过TCMSP和HERB数据库获取芪丹糖肾颗粒的主要成分,利用SwissTargetPrediction数据库获得芪丹糖肾颗粒的作用靶点。通过OMIM,GeneCards,TTD数据库获得疾病作用靶点,采用Venny 2.1软件得到药物作用靶点和疾病作用靶点的共有靶点;使用Cytoscape 3.9.1软件构建“药物-成分-靶点-疾病”网络,使用STRING数据库对共有靶点进行蛋白相互作用(PPI)分析,并使用Cytoscape软件的Network Analyzer功能分析芪丹糖肾颗粒治疗DN的核心成分和核心靶点。利用DAVID数据库对共有靶点进行基因本体论(GO)功能富集及京都基因与基因组百科全书(KEGG)通路富集分析。以药理学实验验证DN模型大鼠中PI3K/Akt信号通路相关蛋白的表达情况。结果共检索出药物主要成分121个,药物作用靶点909个,疾病作用靶点997个,共有靶点107个,拓扑分析得药物治疗DN的核心成分17个。GO功能富集分析得相关功能条目825个,包括生物过程646个,细胞组分81个,分子功能98个,主要包括基因表达的正调控、细胞质膜、蛋白结合等。KEGG通路富集分析共得到通路147条,主要涉及癌症通路、AGE-RAGE信号通路、HIF-1信号通路、PI3K/Akt信号通路等。在药物作用下,DN模型大鼠肾组织匀浆中p-PI3K/PI3K及p-Akt/Akt蛋白表达水平均显著降低(P<0.05)。结论芪丹糖肾颗粒可经过多个作用靶点和多条信号通路干预DN,通过调控PI3K/Akt信号通路改善肾损伤可能是其作用机制之一。Objective To investigate the mechanism of Qidan Tangshen Granules in the treatment of diabetes nephropathy(DN).Methods The main components of Qidan Tangshen Granules were obtained by the TCMSP and HERB databases,and the relevant targets were obtained by the SwissTargetPrediction database.The targets of disease were obtained by the OMIM,GeneCards and TTD databases.The common targets of drug and disease targets were obtained by the Venny 2.1 software.A″drug-component-target-disease″network was constructed by the Cytoscape 3.9.1 software.Protein-protein interaction(PPI)analysis of common targets was performed by the STRING database.The core components and core targets of Qidan Tangshen Granules in the treatment of DN were analyzed by the Network Analyzer function of the Cytoscape software.The gene ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on common targets were performed by the DAVID database.The expression levels of PI3K/Akt signaling pathway-related proteins in DN model rats were verified by the pharmacological experiments.Results A total of 121 main drug components,909 drug targets,997 disease targets and 107 common targets were searched.Topological analysis showed there were 17 core components of Qidan Tangshen Granules in the treatment of DN.GO functional enrichment analysis showed 825 relevant functional entries,including 646 biological processes,81 cellular components,and 98 molecular functions,mainly involving positive regulation of gene expression,cytoplasmic membrane,protein binding and so on.KEGG pathway enrichment analysis showed 147 pathways,mainly involving the cancer pathway,AGE-RAGE signaling pathway,HIF-1 signaling pathway,PI3K/Akt signaling pathway and so on.The expression levels of p-PI3K/PI3K and p-Akt/Akt proteins in kidney tissue homogenate of DN model rats significantly decreased under the drug(P<0.05).Conclusion Qidan Tangshen Granules can intervene in DN through multiple targets and signaling pathways,and the improvemen

关 键 词：芪丹糖肾颗粒 糖尿病肾病 网络药理学 作用机制 动物实验 PI3K/AKT信号通路 

分 类 号：R969.4[医药卫生—药理学]